Phenylketonuria and Alkaptonuria Indian Medical PG Practice Questions and MCQs
Practice Indian Medical PG questions for Phenylketonuria and Alkaptonuria. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 1: Ochronosis is due to the accumulation of?
- A. Homogentisic acid (Correct Answer)
- B. Alkapton
- C. Xanthurenate
- D. Glyoxylate
Phenylketonuria and Alkaptonuria Explanation: ***Homogentisic acid (Correct)***
- **Ochronosis** is a rare genetic disorder characterized by the accumulation of **homogentisic acid** in connective tissues.
- This accumulation results from a deficiency of the enzyme **homogentisate 1,2-dioxygenase**, which is crucial in the catabolism of tyrosine and phenylalanine.
- Clinically presents with dark pigmentation of cartilage, sclera, and other connective tissues.
*Alkapton (Incorrect)*
- While **alkaptonuria** is the disease caused by homogentisic acid accumulation, **alkapton** itself is not the substance that accumulates in tissues in ochronosis.
- **Alkapton** refers to the dark-colored urine observed in patients with alkaptonuria, which is due to the oxidation of homogentisic acid in the urine.
*Xanthurenate (Incorrect)*
- **Xanthurenate** is an intermediate in the metabolism of tryptophan, and its accumulation is associated with certain vitamin B6 deficiencies.
- It is not involved in the pathogenesis of ochronosis or alkaptonuria.
*Glyoxylate (Incorrect)*
- **Glyoxylate** is a metabolic intermediate involved in various pathways, including carbohydrate and amino acid metabolism.
- Accumulation of glyoxylate is associated with **primary hyperoxaluria type 1**, but not with ochronosis.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 2: In phenylketonuria, which substance should be restricted in the diet?
- A. Tyrosine
- B. Phenylalanine (Correct Answer)
- C. Maize
- D. None of the options
Phenylketonuria and Alkaptonuria Explanation: ***Phenylalanine***
- **Phenylketonuria (PKU)** is a genetic disorder where the body cannot effectively metabolize **phenylalanine** due to a deficiency in the enzyme **phenylalanine hydroxylase**.
- Restricting dietary phenylalanine is crucial to prevent the accumulation of toxic byproducts that can lead to severe neurological damage and developmental delays.
*Tyrosine*
- Tyrosine is normally synthesized from phenylalanine. In PKU, this conversion is impaired.
- While phenylalanine must be restricted, tyrosine supplementation is often necessary for individuals with PKU, as it becomes a conditionally essential amino acid.
*Maize*
- Maize (corn) is a carbohydrate-rich food and does not contain high levels of phenylalanine that would necessitate its restriction in PKU.
- Dietary management in PKU focuses on regulating protein intake, as phenylalanine is an amino acid found in proteins.
*None of the options*
- This option is incorrect because phenylalanine must be strictly restricted in the diet of individuals with phenylketonuria to manage the condition effectively.
- Without dietary restriction, the accumulation of phenylalanine can lead to severe and irreversible neurological damage.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 3: In alkaptonuria, deficiency is:
- A. Phosphofructokinase
- B. HMG CoA reductase
- C. Homogentisate oxidase (Correct Answer)
- D. Xanthine oxidase
Phenylketonuria and Alkaptonuria Explanation: ***Homogentisate oxidase***
- **Alkaptonuria** is an autosomal recessive disorder caused by a deficiency of the enzyme **homogentisate 1,2-dioxygenase** (also known as homogentisate oxidase).
- This enzyme is crucial in the **catabolic pathway of tyrosine**, specifically breaking down **homogentisic acid**.
*Phosphofructokinase*
- Deficiency of **phosphofructokinase** (PFK) causes **Tarui's disease** (Glycogen Storage Disease Type VII), affecting **glycolysis**.
- Symptoms include exercise intolerance, muscle pain, and hemolysis, which are unrelated to alkaptonuria.
*HMG CoA reductase*
- **HMG-CoA reductase** is the rate-limiting enzyme in **cholesterol biosynthesis**, and its inhibitors (statins) are used to lower cholesterol levels.
- Its deficiency is not associated with alkaptonuria.
*Xanthine oxidase*
- **Xanthine oxidase** is involved in the catabolism of **purines**, converting hypoxanthine to xanthine and then xanthine to uric acid.
- Its deficiency causes **xanthinuria**, leading to kidney stones, and it is not associated with alkaptonuria.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 4: A patient presents with ochronosis. Which of the following substance accumulates in this condition?
- A. Homogentisic acid (Correct Answer)
- B. Phenylalanine
- C. Tyrosine
- D. Tryptophan
Phenylketonuria and Alkaptonuria Explanation: ***Homogentisic acid***
- Ochronosis (alkaptonuria) is caused by the accumulation of **homogentisic acid** in connective tissues, leading to a dark blue-black discoloration of cartilage, skin, and organs.
- This accumulation results from a deficiency of **homogentisate 1,2-dioxygenase**, an enzyme involved in the metabolism of **tyrosine**.
- The accumulated homogentisic acid polymerizes and deposits in tissues, causing the characteristic pigmentation.
*Phenylalanine*
- Accumulation of **phenylalanine** occurs in **phenylketonuria (PKU)**, not ochronosis.
- PKU is caused by deficiency of phenylalanine hydroxylase and presents with intellectual disability, musty odor, and fair complexion if untreated.
*Tyrosine*
- While ochronosis involves a defect in **tyrosine metabolism**, tyrosine itself does not accumulate in this condition.
- Tyrosine accumulation occurs in **tyrosinemia**, which presents with different clinical features including hepatic dysfunction and renal tubular defects.
*Tryptophan*
- Defects in **tryptophan metabolism** are associated with conditions like **Hartnup disease**, which presents with pellagra-like symptoms, not ochronosis.
- Tryptophan is a precursor for **serotonin** and **niacin (vitamin B3)**.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 5: A patient reports a change in colour of urine on air exposure. All are true about the condition shown below except:
- A. Blackening of urine is accelerated on exposure to sunlight
- B. Alkaptone bodies are deposited in intervertebral disc
- C. Urine Benedict's test is negative (Correct Answer)
- D. The condition is caused by deficiency of homogentisate 1,2-dioxygenase
Phenylketonuria and Alkaptonuria Explanation: ***Urine Benedict's test is negative***
- This is FALSE - Benedict's test is actually **POSITIVE** in alkaptonuria because **homogentisic acid** is a reducing agent.
- Homogentisic acid readily **reduces Benedict's reagent**, giving a positive test result in alkaptonuria patients.
*Blackening of urine is accelerated on exposure to sunlight*
- This is TRUE - **UV light** and sunlight accelerate the **oxidation of homogentisic acid** in urine.
- The characteristic **dark discoloration** occurs more rapidly when exposed to light and air.
*Alkaptone bodies are deposited in intervertebral disc*
- This is TRUE - **Homogentisic acid (alkaptone bodies)** polymerizes to form **ochronotic pigment** deposits.
- These deposits accumulate in **cartilage** including intervertebral discs, causing degenerative changes and spondylosis.
*The condition is caused by deficiency of homogentisate 1,2-dioxygenase*
- This is TRUE - Alkaptonuria is caused by deficiency of **homogentisate 1,2-dioxygenase** enzyme in the **tyrosine metabolic pathway**.
- This enzyme deficiency leads to accumulation of **homogentisic acid** in blood and urine, causing the characteristic symptoms.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 6: A 4-year-old boy of a first-degree consanguineous couple was noted by the parents to have darkening of the urine to an almost black color when it was left standing. He has a normal sibling, and there are no other medical problems. Growth and development to date are normal. Which of the following is most likely to be elevated in this patient?
- A. Methylmalonate
- B. Homogentisate (Correct Answer)
- C. Phenylpyruvate
- D. α-Ketoisovalerate
Phenylketonuria and Alkaptonuria Explanation: ***Homogentisate***
- The darkening of urine upon standing, especially in a child from a consanguineous marriage, is a classic presentation of **alkaptonuria**.
- **Alkaptonuria** is an autosomal recessive disorder caused by a deficiency of **homogentisate 1,2-dioxygenase**, leading to an accumulation of homogentisate.
*Methylmalonate*
- Elevated **methylmalonate** is characteristic of **methylmalonic aciduria**, a disorder of amino acid metabolism.
- This condition typically presents with metabolic acidosis, developmental delay, and feeding difficulties, which are not described here.
*Phenylpyruvate*
- Elevated **phenylpyruvate** is a key finding in **phenylketonuria (PKU)**, an autosomal recessive disorder of phenylalanine metabolism.
- PKU usually presents with severe intellectual disability if untreated, along with a musty odor, none of which are consistent with the patient's symptoms.
*α-Ketoisovalerate*
- Elevated **α-ketoisovalerate** is a diagnostic marker for **maple syrup urine disease (MSUD)**.
- MSUD typically presents in infancy with poor feeding, lethargy, maple syrup odor in urine, and neurological deterioration, which differ from the presented case.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 7: A patient complains of knee pain. Routine investigations are unremarkable and still, the patient is unsatisfied. Urine turns black on standing, what is the enzyme involved?
- A. Methylmalonyl-CoA mutase
- B. Homogentisate oxidase (Correct Answer)
- C. Xanthine oxidase
- D. Tyrosine hydroxylase
Phenylketonuria and Alkaptonuria Explanation: ***Homogentisate oxidase***
- **Homogentisate oxidase** deficiency leads to **alkaptonuria**, where homogentisic acid accumulates and is excreted in urine, turning it black upon standing or exposure to air. The knee pain could be due to **ochronosis**, the deposition of oxidized homogentisic acid in cartilage and connective tissues.
- The unremarkable routine investigations with persistent knee pain suggest a less common metabolic disorder, which is consistent with **alkaptonuria**'s chronic and insidious presentation.
*Methylmalonyl-CoA mutase*
- A deficiency in **methylmalonyl-CoA mutase** causes **methylmalonic acidemia**, a metabolic disorder typically presenting in infancy with neurological symptoms, feeding difficulties, and developmental delay.
- It does not cause urine to turn black on standing or lead to specific joint pain like that seen in ochronosis.
*Xanthine oxidase*
- **Xanthine oxidase** is involved in purine metabolism, and its inhibition (e.g., by allopurinol) is used to treat **gout**.
- While gout can cause knee pain, it is characterized by elevated uric acid and typically responds to conventional treatments and the urine does not turn black.
*Tyrosine hydroxylase*
- **Tyrosine hydroxylase** is the rate-limiting enzyme in catecholamine synthesis, converting tyrosine to L-DOPA.
- Defects in this enzyme are rare and result in neurological disorders, such as **DOPA-responsive dystonia**, and do not cause urine to blacken or lead to direct joint damage.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 8: VMA is excreted in urine in which condition -
- A. Alkaptonuria
- B. Phenylketonuria
- C. Diabetic ketoacidosis
- D. Pheochromocytoma (Correct Answer)
Phenylketonuria and Alkaptonuria Explanation: ***Pheochromocytoma***
- Pheochromocytoma is characterized by excessive secretion of catecholamines, leading to increased levels of **vanillylmandelic acid (VMA)** in the urine.
- It is often associated with symptoms like **hypertension**, palpitations, and sweating due to catecholamine release.
*Alkaptonuria*
- Caused by a deficiency in **homogentisate oxidase**, leading to the accumulation of **homogentisic acid**, not VMA.
- Clinically presents with **dark urine** and can lead to **ochronosis**, but does not involve catecholamines.
*Phenylketonuria*
- A metabolic disorder resulting from a deficiency in **phenylalanine hydroxylase**, leading to elevated levels of **phenylalanine** rather than VMA.
- Symptoms include intellectual disability and musty odor, unrelated to catecholamine metabolism.
*Diabetic ketoacidosis*
- This is a condition caused by severe **insulin deficiency**, resulting in elevated ketone bodies and glucose levels, but does not cause increased VMA excretion.
- Symptoms include **fruity breath**, dehydration, and metabolic acidosis, focusing on ketone production rather than catecholamine metabolism.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 9: Coenzyme for phenylalanine hydroxylase is?
- A. Tetrahydrofolate
- B. Pyridoxal phosphate
- C. S-adenosyl methionine
- D. Tetrahydrobiopterin (Correct Answer)
Phenylketonuria and Alkaptonuria Explanation: ***Tetrahydrobiopterin***
- **Tetrahydrobiopterin (BH4)** is an essential coenzyme for aromatic amino acid hydroxylases, including **phenylalanine hydroxylase (PAH)**.
- PAH converts **phenylalanine** to **tyrosine**, and deficiencies in BH4 or PAH itself lead to *phenylketonuria (PKU)*.
*Tetrahydrofolate*
- **Tetrahydrofolate (THF)** is a coenzyme derived from **folic acid** and is primarily involved in **one-carbon metabolism**, including **purine** and **pyrimidine synthesis**, and various amino acid interconversions.
- It does not directly act as a coenzyme for phenylalanine hydroxylase.
*Pyridoxal phosphate*
- **Pyridoxal phosphate (PLP)**, a derivative of **vitamin B6**, is a crucial coenzyme for many enzymes involved in **amino acid metabolism**, particularly in **transamination**, **decarboxylation**, and side-chain cleavage reactions.
- It is not the coenzyme for phenylalanine hydroxylase.
*S-adenosyl methionine*
- **S-adenosyl methionine (SAM)** is a major **methyl donor** in various biochemical reactions, important for the synthesis of **neurotransmitters**, **hormones**, and **phospholipids**.
- While essential for many metabolic pathways, it is not involved as a coenzyme for phenylalanine hydroxylase.
Phenylketonuria and Alkaptonuria Indian Medical PG Question 10: What is the diagnosis in a patient who presents with nausea and vomiting, initially responds to intravenous glucose, but later develops increased blood glutamine and orotic acid levels?
- A. CPS-I deficiency
- B. Arginino succinate synthetase deficiency
- C. CPS-II deficiency
- D. Ornithine transcarbamoylase deficiency (Correct Answer)
Phenylketonuria and Alkaptonuria Explanation: ***Ornithine transcarbamoylase deficiency***
- **Ornithine transcarbamoylase (OTC) deficiency** is an X-linked urea cycle disorder that leads to the accumulation of **carbamoyl phosphate**.
- This excess carbamoyl phosphate is shunted into pyrimidine synthesis, resulting in increased **orotic acid** and **glutamine** levels, and symptoms like nausea and vomiting due to hyperammonemia.
*CPS-I deficiency*
- **Carbamoyl phosphate synthetase I (CPS-I) deficiency** also causes hyperammonemia but does not involve elevated **orotic acid**, as the pathway leading to pyrimidine synthesis is not overstimulated.
- This deficiency would present with high ammonia and glutamine levels, but **normal or low orotic acid**.
*Arginino succinate synthetase deficiency*
- **Argininosuccinate synthetase deficiency** (citrullinemia) is characterized by very high plasma **citrulline** levels, which are not mentioned in this patient's presentation.
- While it is a urea cycle disorder causing hyperammonemia, the diagnostic marker of elevated citrulline differentiates it from OTC deficiency.
*CPS-II deficiency*
- **Carbamoyl phosphate synthetase II (CPS-II)** is involved in *de novo* pyrimidine synthesis and is not part of the urea cycle.
- A deficiency in CPS-II would typically lead to **pyrimidine starvation** rather than hyperammonemia or elevated orotic acid.
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